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Retinal vein occlusion (RVO) is a common retinal venous disorder that causes vision loss. No specific therapy has been developed. Controversy exists regarding two treatments: intravitreal dexamethasone implants and anti-vascular endothelial growth factor (VEGF). The goal of this study is to compare the effectiveness and safety of dexamethasone implants and anti-VEGF treatment for RVO.
Metronomic cancer chemotherapy has displayed the potential to ameliorate immunosuppressive tumor microenvironment (TME) and facilitate antitumor immunotherapy, but this strategy requires uninterrupted administration of low-dose chemotherapeutic agents and suffers from rapid drug clearance. Here, we developed a single-dose in situ immune stimulator storage to achieve prolonged retention and sustained release of drugs in tumor parenchyma. Importantly, this storage could initiate immune responses through photothermal therapy (PTT) and simultaneously remodel TME. In detail, the storage framework (NGOPC) with size of ~60 nm, was composed of Ala-Ala-Asn-Cys-Lys modified nano graphene oxide (NGO-PEG-pep) and 2-cyano-6-aminobenzothiazole modified NGO (NGO-PEG-CABT), and could sufficiently penetrate into deep tumor region. Once NGOPC arrived at the core field, legumain overexpressing in TME could trigger click cycloaddition reaction of NGO-PEG-pep with NGO-PEG-CABT to form network, leading to aggregation and augmented retention in tumor. Additionally, paclitaxel (PTX) that can block immunologic escape was loaded in NGOPC (NGOPC@PTX), which synergistically worked with PTT-generated antitumor immunity. We found that NGOPC@PTX possessed the superior ability to accumulate in tumor and generate antitumor immunological efficacy by improving immune factors: induction of HSP70-mediated immunogenic cell death, reduction of regulatory T cells, and activation of cytotoxic T lymphocyte. This in situ storage, which exhibited excellent tumor growth inhibition effect and prolonged lifespan in combination with PTT, displays the potential for intensified cancer immunotherapy.
Prunus pedunculata (Prunoideae: Rosaceae), a relic shrub with strong resistance and multiple application values, is endangered in China. Extensive research had been devoted to gene expression, molecular markers, plastid genome analysis, and genetic background investigations of P. pedunculata. However, the mitochondrial genome of this species has not been systematically described, owing to the complexity of the plant mitogenome.
Astragalus is the largest genus in Leguminosae. Several molecular studies have investigated the potential adulterants of the species within this genus; nonetheless, the evolutionary relationships among these species remain unclear. Herein, we sequenced and annotated the complete chloroplast genomes of three Astragalus species-Astragalus adsurgens, Astragalus mongholicus var. dahuricus, and Astragalus melilotoides using next-generation sequencing technology and plastid genome annotator (PGA) tool. All species belonged to the inverted repeat lacking clade (IRLC) and had similar sequences concerning gene contents and characteristics. Abundant simple sequence repeat (SSR) loci were detected, with single-nucleotide repeats accounting for the highest proportion of SSRs, most of which were A/T homopolymers. Using Astragalus membranaceus var. membranaceus as reference, the divergence was evident in most non-coding regions of the complete chloroplast genomes of these species. Seven genes (atpB, psbD, rpoB, rpoC1, trnV, rrn16, and rrn23) showed high nucleotide variability (Pi), and could be used as DNA barcodes for Astragalus sp. cemA and rpl33 were found undergoing positive selection by the section patterns in the coded protein. Phylogenetic analysis showed that Astragalus is a monophyletic group closely related to the genus Oxytropis within the tribe Galegeae. The newly sequenced chloroplast genomes provide insight into the unresolved evolutionary relationships within Astragalus spp. and are expected to contribute to species identification.
Currently, the use of assisted reproductive technology (ART) is increasing. Because of the poor prognosis of retinopathy of prematurity (ROP), the association between ART and the ROP has been explored in several studies, but the result was still inconclusive. Conducting a meta-analysis, we evaluated the risk of ROP in relation to the ART. Subgroup analysis as well as groups with different embryo numbers and different ROP stages was further analyzed. The PubMed, Embase, and Cochrane Library databases were searched for studies recording data about both the use of ART and ROP occurrence simultaneously. Odds ratios (ORs) and 95% confidence interval (95%CI) were calculated to analyze the association by using random- or fixed-effect models based on heterogeneity test. In total 15 observational studies containing 10392 ART cases and 39474 spontaneous conception cases were included. Results showed that there was a significant association between the use of ART and ROP occurrence in the offspring (OR = 1.34, 95% CI: 1.05 to 1.73, P = 0.02). With subgroup analysis, we found that the influence actually came from a subgroup of ART, the in vitro fertilization (IVF). Moreover, there was a significant association between ART and ROP in singletons. Though insignificant, the ORs were larger than 1 in the analysis between ART and stage 1 and 2 ROP. But ART showed significant association with stage 3 ROP. Our study preliminarily indicated that the use of IVF was associated with higher risk of ROP occurrence. And ART is more likely to result in severe ROP and ROP in singletons. Further specific, high-quality studies with large sample size are still needed to draw more precise conclusion.
Background. Wushenziye formula (WSZYF) is an effective traditional Chinese medicine in the treatment of type 2 diabetes mellitus (T2DM). Aim. This study aimed to identify the effects and underlying mechanisms of WSZYF on improving skeletal muscle insulin resistance in T2DM. Methods. An animal model of T2DM was induced by Goto-Kakizaki diabetes prone rats fed with high fat and sugar for 4 weeks. Insulin resistance model was induced in skeletal muscle cell. Results. In vivo, WSZYF improved general conditions and decreased significantly fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, insulin concentration, and insulin resistance index of T2DM rats. In vitro, WSZYF enhanced glucose consumption in insulin resistance model of skeletal muscle cell. Furthermore, WSZYF affected the expressions of molecules in regulating T2DM, including increasing the expressions of p-IRS1, p-Akt, and GLUT4, reducing PTP1B expression. Conclusion. These findings displayed the potential of WSZYF as a new drug candidate in the treatment of T2DM and the antidiabetic mechanism of WSZYF is probably mediated through modulating the PTP1B-IRS1-Akt-GLUT4 signaling pathway.
This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injections. Diabetic model rats were randomly divided into 5 groups: the model control group, the metformin group, and Modified Sanzi Yangqin Decoction groups of low, medium, and high doses. OGTT was conducted every two weeks during treatment period. At the end of the treatment, the fasting blood glucose (FBG) level and the fasting C-peptide level were measured to calculate insulin resistance index. The levels of IRS-1, p-IRS-1(Tyr895), and protein tyrosine phosphates 1B (PTP1B) in skeletal muscle were also measured. Modified Sanzi Yangqin Decoction significantly reduced the FBG level, increased the fasting C-peptide level, and lowered the insulin resistance index in type 2 diabetic rats. It also significantly increased the protein level of p-IRS-1(Tyr895) and reduced the PTP1B protein level in skeletal muscle of type 2 diabetic rats. Modified Sanzi Yangqin Decoction increases tyrosine phosphorylation of IRS-1 in skeletal muscle of type 2 diabetic rats, which results from the increase of p-IRS-1(Tyr895) protein and is related to the suppression of PTP1B protein.
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